TY - JOUR
T1 - Postprandial insulin profiles with implantable pump therapy may explain decreased frequency of severe hypoglycemia, compared with intensive subcutaneous regimens, in insulin-dependent diabetes mellitus patients
AU - Nathan, David M.
AU - Dunn, Frederick L.
AU - Bruch, John
AU - McKitrick, Charles
AU - Larkin, Mary
AU - Haggan, Coral
AU - Lavin-Tompkins, Jodi
AU - Norman, Dennis
AU - Rogers, David
AU - Simon, Deborah
N1 - Funding Information:
From the Diabetes Research Center, Diabetes Unit (DMN, CM, ML, CH, DN, DR, DSJ, and Departments of Medicine (DMN) and Psychology (DN), Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; and the Division of Endocrinology, Metabolism, and Nutrition, Department of Medicine, Duke Universrty Medical Center, Durham, North Carolina (FLD, JB, JLT). Supported by a research grant from Infusaid, Inc., and through the General Cknrcal Research Center Program of the National Center of Research Resources, National Institutes of Health (Massachusetts General Hospital RR-01066, Duke Unwersity MOl-RR-30). Requests for reprints should be addressed to David M. Nathan, MD, Diabetes Unrt, Massachusetts General Hospital, Boston, Massachusetts 02114. Manuscript submitted June 26, 1995 and accepted In revised form October 13, 1995.
PY - 1996/4
Y1 - 1996/4
N2 - PURPOSE: To examine the mechanism of the decreased frequency of severe hypoglycemia with implantable pump therapy compared with subcutaneous intensive therapy. PATIENTS AND METHODS: Eight subjects with insulin-dependent diabetes mellitus (IDDM), enrolled in an implantable insulin pump study, were admitted to the General Clinical Research Center and on 2 separate days were given either a dose of preprandial insulin chosen to maintain normoglycemia for a standard (450 kcal, 50% carbohydrate) breakfast or 1.75 times the dose. The two doses were administered subcutaneously (by syringe or with an external pump) during one inpatient admission and by implantable pump (intraperitoneally, n = 6; or intravenously, n = 2) during a separate admission. Blood glucose, plasma-free insulin, and neurocognitive function were measured for 4 hours after the meal. RESULTS: Subcutaneous administration resulted in 7 episodes of hypoglycemia (2 with the usual dose and 5 with the 1.75-fold dose), defined as blood glucose less than 50 mg/dL; implantable pump treatment resulted in only 2 episodes, both with the 1.75-fold dose (P <0.05, Fisher's two-tailed test for implantable versus subcutaneous). Compared with subcutaneous delivery, implantable pump therapy provided significantly lower insulin levels during the final 2 hours after administration of the usual dose and the 1.75-fold dose (P <0.005). In addition to the decreased frequency of hypoglycemia, implantable pump therapy resulted in significantly lower area under the glycemia curve during the first 120 minutes with the 1.75-fold dose compared with subcutaneous administration. CONCLUSIONS: The lower frequency of severe hypoglycemia with intensive therapy administered by implantable pump therapy is explained by the more rapid clearance of insulin delivered intraperitoneally or intravenously compared with intensive subcutaneous injection regimens. The lower frequency of severe hypoglycemia with implantable pump therapy compared with subcutaneous therapy demonstrated in clinical trials is confirmed by this study, in which we attempted to induce hypoglycemia.
AB - PURPOSE: To examine the mechanism of the decreased frequency of severe hypoglycemia with implantable pump therapy compared with subcutaneous intensive therapy. PATIENTS AND METHODS: Eight subjects with insulin-dependent diabetes mellitus (IDDM), enrolled in an implantable insulin pump study, were admitted to the General Clinical Research Center and on 2 separate days were given either a dose of preprandial insulin chosen to maintain normoglycemia for a standard (450 kcal, 50% carbohydrate) breakfast or 1.75 times the dose. The two doses were administered subcutaneously (by syringe or with an external pump) during one inpatient admission and by implantable pump (intraperitoneally, n = 6; or intravenously, n = 2) during a separate admission. Blood glucose, plasma-free insulin, and neurocognitive function were measured for 4 hours after the meal. RESULTS: Subcutaneous administration resulted in 7 episodes of hypoglycemia (2 with the usual dose and 5 with the 1.75-fold dose), defined as blood glucose less than 50 mg/dL; implantable pump treatment resulted in only 2 episodes, both with the 1.75-fold dose (P <0.05, Fisher's two-tailed test for implantable versus subcutaneous). Compared with subcutaneous delivery, implantable pump therapy provided significantly lower insulin levels during the final 2 hours after administration of the usual dose and the 1.75-fold dose (P <0.005). In addition to the decreased frequency of hypoglycemia, implantable pump therapy resulted in significantly lower area under the glycemia curve during the first 120 minutes with the 1.75-fold dose compared with subcutaneous administration. CONCLUSIONS: The lower frequency of severe hypoglycemia with intensive therapy administered by implantable pump therapy is explained by the more rapid clearance of insulin delivered intraperitoneally or intravenously compared with intensive subcutaneous injection regimens. The lower frequency of severe hypoglycemia with implantable pump therapy compared with subcutaneous therapy demonstrated in clinical trials is confirmed by this study, in which we attempted to induce hypoglycemia.
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U2 - 10.1016/S0002-9343(97)89516-2
DO - 10.1016/S0002-9343(97)89516-2
M3 - Article
C2 - 8610727
AN - SCOPUS:0030007999
SN - 0002-9343
VL - 100
SP - 412
EP - 417
JO - American Journal of Medicine
JF - American Journal of Medicine
IS - 4
ER -